Recently we have mapped the c-ets locus in humans onto two separate chromosomes 11 and 21. For convenience we have named these proto-oncogene loci ets-1, located on chromosome 11, and ets-2, located on chromosome 21. Given the known correlation of many forms of human cancers to specific chromosomal aberrations, we are using our distinct probes to investigage the involvement of the ets proto-oncogenes in the pathogenesis of certain suspect leukemia malignancies. A number of these human leukemias, such as the acute undifferentiated leukemias (AUL) and the acute myeloid leukemia with maturation (AML-M2), show specific chromosomal aberrations involving the chromsomes known to contain the ets-1 and ets-2 proto-oncogene loci. We have identified, in a number of human cells from these actue leukemia patients, chromosomal aberrations such as deletions and translocations involving the 11q23.3 and 21q22 bands, specifically. The expression ofc-ets is being investigated in an effort to determine if there are any qualitative and/or quantitative changes. Further, since Down's syndrome is associated with trisomy 21 aberrations, and these individuals also have an elevated incidence of acute leukemia, probing cells isolated from these individuals with the proto-oncogenes ets may illuminate any molecular basos for this coincidence.